Abstract

The proteolytic processing of collagen (collagenolysis) is critical in development and homeostasis, but also contributes to numerous pathologies. Mammalian interstitial collagenolytic enzymes include members of the matrix metalloproteinase (MMP) family and cathepsin K. While MMPs have long been recognized for their ability to catalyze the hydrolysis of collagen, the roles of individual MMPs in physiological and pathological collagenolysis are less defined. The use of knockout and mutant animal models, which reflect human diseases, has revealed distinct collagenolytic roles for MT1-MMP and MMP-13. A better understanding of temporal and spatial collagen processing, along with the knowledge of the specific MMP involved, will ultimately lead to more effective treatments for cancer, arthritis, cardiovascular conditions, and infectious diseases. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.

Schematic representation of MMP and cathepsin K cleavage sites in type I collagen. The bold, solid green arrow indicates the known MMP cleavage site (bond 775–776) aligned in all three chains in the triple-helix. The bold, dashed green arrows indicate the cathepsin K cleavage sites where all three chains in the triple-helix align (bonds 9–10 and 21–22; see ). The dashed green arrows indicate the cathepsin K cleavage sites in individual collagen chains that do not align within the triple-helix (see ). For cleavage by cathepsin K within individual chains, sites in the α1(I) chain are noted above the triple-helix, while cleavage sites in the α2(I) chain are noted below the triple-helix.